Background Currently, several systems of dentin substrate-reacting adhesives are available for use in the restorative treatment against caries. However, the bond effectiveness and property of different adhesive systems to caries-affected dentin are not fully understood. The objective of this study was to evaluate the bond strength of different adhesives to both normal dentin (ND) and caries-affected dentin (CAD) and to analyze the dentin/adhesive interracial characteristics.Methods Twenty eight extracted human molars with coronal medium carious lesions were randomly assigned to four groups according to adhesives used. ND and CAD were bonded with etch-and-rinse adhesive Adper~(TM) Single Bond 2 (SB2) or self-etching adhesives Clearfil SE Bond (CSE), Clearfil S~3 Bond (CS3), iBond GI (IB). Rectangular sticks of resin-dentin bonded interfaces 0.9 mm~2 were obtained. The specimens were subjected to microtensile bond strength (μTBS) testing at a crosshead speed of 1 mm/min. Mean μTBS was statistically analyzed with analysis of variance (ANOVA) and Student-Newman-Keuls tests. Interfacial morphologies were analyzed by Scanning Electron Microscopy (SEM).Results Etch-and-rinse adhesive Adper~(TM) Single Bond 2 yielded high bond strength when applied to both normal and caries-affected dentin. The two-step self-etching adhesive Clearfil SE Bond generated the highest bond strength to ND among all adhesives tested but a significantly reduced strength when applied to CAD. For the one-step self-etching adhesives, Clearfil S~3 Bond and iBond GI, the bond strength was relatively low regardless of the dentin type. SEM interfacial analysis revealed that hybrid layers were thicker with poorer resin tag formation and less resin-filled lateral branches in the CAD than in the ND for all the adhesives tested.Conclusion The etch-and-rinse adhesive performed more effectively to caries-affected dentin than the self-etching adhesives.